This invention relates to a crosslinked glycosaminoglycan. More particularly, it is concerned with a crosslinked glycosaminoglycan or salt thereof, which is prepared by crosslinking a glycosaminoglycan (hereinafter referred to as "GAG") or a salt thereof with a polyfunctional epoxy compound.
As GAG which has been hitherto found in this field, there may be mentioned as non-sulfated GAG hyaluronic acid and chondroitin (hereinafter referred to as "Ch"), while there are known as sulfated GAG chondroitin sulfate (hereinafter referred to as "ChS"), heparin (hereinafter referred to as "Hep"), heparan sulfate (hereinafter referred to as "HS"), keratan sulfate (hereinafter referred to as "KS"), and keratanpolysulfate (hereinafter referred to as "KPS"). Also, ChS may includes ChS-A, ChS-B, ChS-C, Ch-S, ChS-E, ChS-F and ChS-H.
It has been recently elucidated that such GAG's may participate in development, growth, aging or diseased state of various tissues or cells and play an important role, respectively. Generally, it has been reported that GAG has functions of (1) control of water or electrolytes in extracellular fluids, (2) calcification, (3) fibrosis, (4) wound healing and granulation, (5) infection resistance, (6) lubrication, (7) anticoagulation and antilipemia, (8) maintenance of transparency and others.
In order that those functions of GAG itself as depicted above may be developed, there has been attempted external administration of GAG to a living body. However, only a weak effect could be sometimes attained, no effect could be observed or an effect could be developed at an undesired or inconvenient site or portion in some instances. The reasons therefor are believed to be the facts that the GAG externally administered had a lower molecular weight during its purification procedures than that when present in a living body, and the GAG did not form any inherent protein complex in a living body, thereby the GAG being very soluble in water and easily subjected to enzymatic decomposition, and then the GAG would disappear before development of its functions without any retention at local sites or diffuse into other inconvenient sites.
For solving such disadvantageous problems, there have been proposed that GAG be bound to an amino acid, a peptide, a protein or the like or combined with a suitable fat-soluble group. However, any one of them has not yet been practically embodied in view of antigenicity or a quite different property developed.
On the other hand, it has been suggested to crosslink dextran or agarose with a crosslinking agent as disclosed in Japanese Patent Published Application No. Sho 47-1321 (or No. 1321/1972); there has not, however, been reported any instance crosslinking GAG, for the purpose of solving above-mentioned disadvantages.
Under these circumstance, we have made earnest studies to obtain a crosslinked GAG having resistance to enzymatic decomposition and, as a result, it has been found that the intended objects can be achieved by crosslinking GAG or a salt thereof with a polyfunctional epoxy compound Further, it has been found that the present crosslinked GAG or salts thereof can have a wide variety of medical and cosmetic uses.